The Affected-Pedigree-Member Method: Power to Detect Linkage

Weeks, Daniel E.; Harby, Lisa D.

doi:10.1159/000154250

Cited by 72 publications

(91 citation statements)

References 10 publications

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“…The data were also analyzed nonparametrically using the Affected-Pedigree-Member method (APM) 29 and a modified APM statistic. 30 In the modified method (GPM), the test statistic is extended to include contrast between affected and unaffected pedigree members.…”

Section: Discussionmentioning

confidence: 99%

Catechol-O-methyltransferase and Gilles de la Tourette syndrome

1999

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Gilles de la Tourette syndrome (TS) is a neuropsychiatric disorder characterized by both motor and vocal tics. Individuals with TS often have symptoms of obsessive compulsive disorder (OCD) and these symptoms are thought to be an alternative expression of the TS gene(s) in TS families. In this paper we test for linkage of the functional polymorphism in the catechol-Omethyltransferase (COMT) gene to TS and OCD in five multi-generational families ascertained through a TS proband. This polymorphism (valine to methionine at codon 158) has been previously reported to influence the activity of COMT by three to four-fold and has recently been reported to be associated with OCD. 1 We tested for linkage using an autosomal dominant model with reduced penetrance and non-parametric methods. No significant evidence for linkage was found for the COMT gene and the TS/CMT, or OCD phenotypes in these pedigrees.

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Section: Discussionmentioning

confidence: 99%

Catechol-O-methyltransferase and Gilles de la Tourette syndrome

1999

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“…The NPL pairs statistic [Weeks and Lange, 1988] was used to test for increased allele sharing among affected individuals. The genotyped sample consisted of 3,944 individuals from 841 nuclear families.…”

Section: Linkage Analysismentioning

confidence: 99%

A genome‐wide linkage scan provides evidence for both new and previously reported loci influencing common migraine

Ligthart

Nyholt

Hottenga

et al. 2008

American J of Med Genetics Pt B

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Latent class analysis was performed on migraine symptom data collected in a Dutch population sample (N ¼ 12,210, 59% female) in order to obtain empirical groupings of individuals suffering from symptoms of migraine headache. Based on these heritable groupings (h 2 ¼ 0.49, 95% CI: 0.41-0.57) individuals were classified as affected (migrainous headache) or unaffected. Genomewide linkage analysis was performed using genotype data from 105 families with at least 2 affected siblings. In addition to this primary phenotype, linkage analyses were performed for the individual migraine symptoms. Significance levels, corrected for the analysis of multiple traits, were determined empirically via a novel simulation approach. Suggestive linkage for migrainous headache was found on chromosomes 1 (LOD ¼ 1.63; pointwise P ¼ 0.0031), 13 (LOD ¼ 1.63; P ¼ 0.0031), and 20 (LOD ¼ 1.85; P ¼ 0.0018). Interestingly, the chromosome 1 peak was located close to the ATP1A2 gene, associated with familial hemiplegic migraine type 2 (FHM2). Individual symptom analysis produced a LOD score of 1.97 (P ¼ 0.0013) on chromosome 5 (photo/ phonophobia), a LOD score of 2.13 (P ¼ 0.0009) on chromosome 10 (moderate/severe pain intensity) and a near significant LOD score of 3.31 (P ¼ 0.00005) on chromosome 13 (pulsating headache). These peaks were all located near regions previously reported in migraine linkage studies. Our results provide important replication and support for the presence of migraine susceptibility genes within these regions, and further support the utility of an LCA-based phenotyping approach and analysis of individual symptoms in migraine genetic research. Additionally, our novel ''2-step'' analysis and simulation approach provides a powerful means to investigate linkage to individual trait components.

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“…Analyses were also performed with the nonparametric Affected Pedigree Member (APM) method of linkage analysis method 25 that examines the degree of allele sharing among all affected individuals. This method was chosen over other nonparametric methods because only nine affected sibling pairs with DNA ruled out sib pair methods, and large family size ruled out GeneHunter NPL analyses.…”

Section: Linkage Analysismentioning

confidence: 99%

Evidence for a chromosome 2p13–14 schizophrenia susceptibility locus in families from Palau, Micronesia

et al. 1998

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A large multiplex schizophrenia pedigree ascertained from the Micronesian nation of Palau was genotyped with 406 microsatellite DNA markers evenly distributed throughout the genome. Assuming autosomal dominant inheritance, the highest genome-wide lod scores were found for DNA loci mapping to 2p13-14; the maximum lod score was 2.17 (theta = 0.05) at D2S441. A nonparametric APM analysis was also suggestive at D2S441 (APM score = 2.96, P = 0.011). Of the 14 affected cases in this extended family, eight share a large haplotype in this region spanning ෂ11 cM. When 16 other families containing 65 schizophrenic cases were typed in a follow-up study of this region, the maximum lod score remained positive (maximum at D2S441 1.69, theta = 0.20). APM results also remained positive at D2S441 for all 17 families (APM score = 4.87, P = 0.0006). The linkage and haplotype sharing results provide suggestive evidence for a 2p locus predisposing to schizophrenia in a subset of families in the Palauan population.

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The Affected-Pedigree-Member Method: Power to Detect Linkage

Cited by 72 publications

References 10 publications

Catechol-O-methyltransferase and Gilles de la Tourette syndrome

Catechol-O-methyltransferase and Gilles de la Tourette syndrome

A genome‐wide linkage scan provides evidence for both new and previously reported loci influencing common migraine

Evidence for a chromosome 2p13–14 schizophrenia susceptibility locus in families from Palau, Micronesia

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